tbuckley/cabot-search huggingface dataset:
The effect of inflammatory-nutri̇tional prognosti̇c scori̇ng (INPS) system on treatment response and prognosi̇s i̇n pati̇ents wi̇th locally advanced gastroesophageal juncti̇on and gastri̇c cancer wi̇th neoadjuvant systemi̇c treatment.
Authors: Merve Keskinkilic, Femin Yalcin, Tolga Gozmen, Hulya Ellidokuz, Tugba Yavuzsen, Ilhan Oztop
Journal: Journal of Clinical Oncology (2023)

e16092 Background: We aimed to reveal the prognostic value of inflammatory-nutritional prognostic score (INPS), which is a new scoring system created by using frequently used immune-nutritional markers, as a biomarker, on nutrition and immune status in patients with locally advanced GEJ and gastric cancer. Methods: Patients who were treated in Dokuz Eylul University Medical Oncology Department between 2010-2022 years and diagnosed with locally advanced GEJ and gastric cancer and receiving NACT were included in this study retrospectively. We selected the most valuable biomarkers (Albumin, ABR, CRP, CAR, De-Ritis, HALP, MLR, NLR, PLR, PNI, SII) to develop INPS by the least absolute shrinkage and selection operator (LASSO) Cox regression model. A prognostic nomogram incorporating INPS and other independent clinicopathological factors was developed based on the stepwise multivariate Cox regression method. The retained features with nonzero coefficients were used to establish a novel INPS. The selected four biomarkers were used to construct the novel INPS for our patients. Results: Median follow-up time of 101 patients was 16.7 months (95% CI= 3.7-73.7), DFS was 20.5 months (95%CI= 16.2-24.8 ), OS was 36.6 months (95%CI=25.4-47.8). The 101 patients in the study were randomly assigned to train (n = 71) and test (n = 30) sets in a 7:3 ratio. Using the LASSO Cox regression model, four inflammatory-nutritional biomarkers (INB) with nonzero coefficients, namely, PLR, DeRitis, PNI and LAR, of the 13 parameters were selected. The LASSO coefficient profiles of the 13 INB and 10-fold cross-validation for tuning parameter selection in the LASSO model were presented. The optimal cut-off values for these four biomarkers based on disease-free survival were determined using the Maximally Selected Rank Statistics. The respective cut-off values for PLR, DeRitis, PNI, and LAR were obtained to be 107.93, 1.75, 33.92, and 58.17. Both the patients in the Train set and the in the Test set were classified as low-risk (INPS score ≤ 1) and high-risk (INPS score &gt;1) groups. There was a statistically significant difference in survival probabilities between low and high risk groups in both groups (respectively; p=0.009, p=0.029). A prognostic nomogram including INPS and other independent clinicopathological factors was developed. Conclusions: The search for biomarkers with prognostic value in GEJ and gastric adenocarcinoma receiving NACT continues. With this study, it has been shown for the first time in the literature that the new screening system, INPS, created with nutritional and inflammatory markers, can be used as a prognostic tool to predict disease-free survival in this patient group.
The preventive effect of celecoxib on regorafenib-associated hand-foot syndrome in patients with liver metastasis from colorectal cancer: A single-center, retrospective, real-world study.
Authors: Lijun Wang, Hongwei Wang, Wei Liu, Kemin Jin, Quan Bao, Kun Wang, Baocai Xing
Journal: Journal of Clinical Oncology (2023)

e15576 Background: Regorafenib, an oral multi-kinase inhibitor, is the third- or later-line therapy for colorectal cancer with liver metastasis (CRLM), but the hand-foot syndrome (HFS) is its most common adverse reaction. Celecoxib, a selective COX-2 inhibitor, can treat inflammation. This study aimed to explore whether additing celecoxib to the cancer therapy regorafenib can prevent or alleviate the HFS, improve drug tolerance, and prolong the patient’s survival. Methods: In the retrospective cohort analysis, patients with colorectal cancer and liver metastasis, to whom regorafenib and celecoxib were administered in the Department of Hepatopancreatobiliary Surgery of Beijing Cancer Hospital between November 2021 and October 2022, were included. Upon the medical records from physical examination and other means of follow-ups, the Kaplan-Meier estimator analyzed the survival function and the severity of adverse events was described according to the CTCAE v.5.0 standards. Results: Twenty-six patients were included in the analysis and 14 colorectal cancer patients had extrahepatic metastases at the onset of the treatment. All patients received regorafenib and celecoxib. Further, 15 patients were treated with a combination of immune checkpoint inhibitors, 3 patients underwent combined local-regional therapy, 1 patient received combined chemotherapy, and 7 patients received regorafenib. Among all the patients, the incidence of grades 1 &amp; 2 HFS was 46% and no grade 3 HFS was observed. The other main adverse events were hoarseness (35%), fatigue (27%), rash (27%), and neutropenia (15%). The most frequent adverse events from the CONCUR study and current analysis are shown in Table 1. Five patients (19%) had their treatment interrupted or their drug dose reduced due to adverse events. The median follow-up time of all patients was 5.3 (range, 1.6-13.1) months, the overall survival was not reached, and the median progression free survival was 2.9 (95% CI: 1.5-4.3) months. As the overall response in all patients after treatment, 3 cases (12%) achieved PR, 11 cases (42%) had SD and 12 cases (46%) showed PD. Conclusions: The addition of celecoxib to the cancer-line therapy regorafenib in CRLM patients did not reduce the incidence of HFS, but reduced the severity of HFS (grade 3). Also, it did not shorten the survival time of the patients. The addition of celecoxib to the main therapy might alleviate some adverse effects. [Table: see text]
Evaluating racial disparities for patients with advanced hepatocellular carcinoma (HCC) receiving first line immunotherapy within an equal access system.
Authors: Lauren Diaz Boyle, Munaf Alkadimi, Maria Elena Fierro, Kana Lucero, Kathleen Franklin, Michael Mader, Zohra Nooruddin
Journal: Journal of Clinical Oncology (2023)

4109 Background: The incidence and mortality of HCC are increasing in the USA. HCC disparities have been reported across the entirety of the cancer timeline, from screening to local and systemic treatment and liver transplant. We aim to analyze the clinical characteristics, outcomes, and racial disparities in patients with advanced HCC receiving first-line Atezolizumab plus Bevacizumab (A+B) in the Veterans Health Administration (VHA) – the only health care system in the USA that provides equal access to all patients. Methods: Patients were followed from their A+B initiation date through the earliest of the last VHA visit, loss to follow-up, death, or end of study on Jan 31, 2023. Structured electronic health record and chart review data were retrospectively collected to determine patient baseline characteristics, including self-reported race, number of A+B doses, treatment response, subsequent line of treatment, length of follow-up, and overall survival (OS). The Chi-Squared test was used to compare rates, and Mann-Whitney test was used to compare medians. Results: Three hundred twenty-five patients were included. 64% were non-Hispanic White (NHW), and 36% were all other (AO) ethnicities or races combined (26% Black, 8% Hispanic, 2% Asian or Indigenous). The median age for each cohort was similar (66 years for AO vs. 68 for NHW), and ECOG performance was &lt;1 in nearly 90% of each cohort. Viral hepatitis accounted for 70% and 48% of AO and NHW, respectively (p=0.0001). Despite clinical differences in OS and progression free survival (PFS), they were not statistically significant. Conclusions: Our VHA real-world data shows that despite having statistically significant etiologies, there was no statistically significant difference in the PFS and OS of patients with advanced HCC receiving first-line A+B in an equal access care system. This study supports our group’s findings in other malignant cohorts within VHA where equal healthcare access can mitigate other socio-demographic and biological factors. [Table: see text]
Mini-hyper-CVD plus inotuzumab ozogamicin (InO), with or without blinatumomab (Blina), in older patients with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (ALL): Updates from a phase II trial.
Authors: Cedric Christophe Nasnas, Elias Jabbour, Fadi Haddad, Nicholas James Short, Lewis Fady Nasr, Walid Macaron, Marianne Zoghbi, Farhad Ravandi, Nitin Jain, Tapan M. Kadia, Naval Guastad Daver, Gautam Borthakur, Courtney Denton Dinardo, Jovitta Jacob, Edith Roy, Christopher Loiselle, Anna Milton, Juan Rivera, Rebecca Garris, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2023)

e19025 Background: The overall survival (OS) of patients (pts) with relapsed/refractory B-ALL has improved with the introduction of InO and Blina. Compared to conventional chemotherapy, the incorporation of these agents into the frontline setting of older pts with ALL may allow the use of less chemotherapy and potentially improve outcomes. Methods: Adults ≥60 yrs with newly diagnosed Ph-negative B-ALL received mini-Hyper-CVD (mini-HCVD) for up to 8 cycles. Initially, InO was given at 1.3-1.8mg/m 2 on Day (D) 3 of Cycle (C) 1 and 0.8-1.3mg/m 2 on D3 of C2-4. Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles. Responders received POMP maintenance for up to 3 yrs. Beginning with pt #50, InO was given in fractionated doses each cycle (0.6 mg/m 2 on D2 and 0.3 mg/m 2 on D8 of C1; 0.3 mg/m 2 on D2 and 8 of C2-4) and 4 cycles of Blina were given following 4 cycles of mini-HCVD plus InO. Maintenance was with 12 cycles of POMP and 4 cycles of Blina (1 cycle of Blina after 3 cycles of POMP). Results: 83 pts were treated, of whom 6 were in complete remission (CR) at enrollment(Table 1). Among 77 evaluable pts, 76 (99%) responded (CR, 90%). Among responders, the rates of MRD negativity by flow cytometry were 79% and 94% after C1 and overall, respectively. No early death was observed. Among 82 pts in remission, 11 (13%) relapsed, 4 (5%) underwent ASCT, 34 (41%) remain in ongoing continuous remission, 33 (41%) died in remission, of whom 9 died after developing MDS/AML. Three pts (4%) developed veno-occlusive disease, 2 after subsequent ASCT. After a median follow-up of 65 months (range, 6-126), the 5-yr continuous remission duration and OS rates were 78% and 48%, respectively. Age ≥70 and adverse cytogenetics were associated with worse outcomes. The inferior outcome in pts ≥70 yrs was primarily attributed to higher rates of death in CR. The 5-yr OS for pts age 60-69 yrs without adverse cytogenetics (n=40), age 60-69 with adverse cytogenetics (n=15), age ≥70 without adverse cytogenetics (n=24) and age ≥70 with adverse cytogenetics (n=4) were 72%, 27%, 38% and 0%, respectively. Conclusions: Favorable outcomes were observed in older pts with newly diagnosed Ph-negative ALL treated with mini-HCVD plus InO, with or without Blina. The 5-yr OS was 48%. Clinical trial information: NCT01371630 . [Table: see text]
CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma.
Authors: Yi Lin, Thomas G. Martin, Saad Zafar Usmani, Jesus G. Berdeja, Andrzej J. Jakubowiak, Mounzer E. Agha, Adam D. Cohen, Abhinav Deol, Myo Htut, Alexander M. Lesokhin, Nikhil C. Munshi, Elizabeth O'Donnell, Carolyn Chang Jackson, Tzu-min Yeh, Arnob Banerjee, Enrique Zudaire, Deepu Madduri, Christopher delCorral, Lida Bubuteishvili-Pacaud, Sundar Jagannath
Journal: Journal of Clinical Oncology (2023)

8009 Background: Heavily pretreated patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with standard of care therapy have median overall survival (OS) of ~12 months (mo). In the single-arm, phase 1b/2 CARTITUDE-1 study (NCT03548207), pts received a single infusion of ciltacabtagene autoleucel (cilta-cel), a CAR-T cell therapy targeting BCMA. At the final protocol-specified analysis (27.7-mo median follow-up [MFU]), overall response rate (ORR) was 98%, with 83% stringent complete response (CR); 27-mo rates of progression-free survival (PFS) and OS were 55% and 70%, respectively. Here, we report study closeout results. Methods: Eligible pts received ≥3 prior lines of therapy (LOT) or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD); and had received prior PI, IMiD, and anti-CD38 antibody therapy. Primary endpoint was ORR and safety; secondary endpoints included PFS, OS, and minimal residual disease (MRD) negativity at 10 -5 . Results: 97 pts received cilta-cel (median age 61 years [y]; median 6 prior LOT; 42% penta-drug refractory; 88% triple-class refractory; 99% refractory to last LOT). As of October 14, 2022, MFU was 33.4 mo (range, 1.5-45.2). Median (m) duration of response was 33.9 mo (95% CI, 25.5–not estimable [NE]). mPFS was 34.9 mo (95% CI, 25.2–NE), with an estimated 47.5% progression free and alive at 36 mo. mOS was not reached (NR), with an estimated 62.9% survival at 36 mo. Of 49 MRD-evaluable pts, 26 had MRD negativity sustained for ≥12 mo, of which 20 had sustained MRD-negative ≥CR. mPFS was NR in these subgroups (Table). 18 pts were MRD negative with ≥CR at 24 mo post infusion. No new safety signals and no new neurotoxicity events were reported since the 27.7-mo MFU. 6 new cases of second primary malignancy were reported, including 2 cases of basal cell carcinoma and 1 case each of myelodysplastic syndrome, B-cell lymphoma, melanoma, and prostate cancer. 5 additional deaths occurred (progressive disease [PD], n=3; pneumonia and sepsis, n=1 each [both unrelated to cilta-cel]), for a total of 35 (PD, n=17; unrelated to cilta-cel, n=12; related, n=6). Conclusions: Longer mPFS was observed after a single infusion of cilta-cel than any previously reported therapy in heavily pretreated pts with RRMM. Achieving CR and/or sustained MRD negativity was associated with prolonged PFS. Pts continue to be followed for safety and survival in the 15-y CARTINUE long-term study (NCT05201781; MMY4002). Clinical trial information: NCT03548207 . [Table: see text]
Phase I/II trial of durvalumab plus tremelimumab and stereotactic body radiotherapy for metastatic head and neck carcinoma: Final results.
Authors: Houda Bahig, Francine Aubin, Phuc Felix Nguyen-Tan, Denis Soulieres, Brock John Debenham, Danielle Charpentier, David A. Palma, Eric Winquist, Rahima Jamal, Khalil Sultanem, Olivier Ballivy, Edith Filion, Tyler Pittman, Manjula Maganti, Philip Wong
Journal: Journal of Clinical Oncology (2023)

6050 Background: Anti-PD-1/PD-L1 is now part of first line therapy in metastatic head and neck squamous cell carcinoma (HNSCC). Stereotactic radiotherapy (SBRT) to metastatic lesions can reduce tumor burden and could be immune-stimulatory. The combination of SBRT with dual-checkpoint blockade with Durvalumab (D, anti-PD-L1) and Tremelimumab (T, anti-CTLA-4) has not previously been tested in HNSCC. We report on the safety and efficacy of this triple treatment combination (TTC) consisting of SBRT sandwiched between cycles of D and T in oligometastatic HNSCC. Methods: This is a phase I/II single arm multi-institutional study powered for 35 patients with oligometatastatic HNSCC (2-10 lesions) (NCT03283605). D (1500 mg) and T (75 mg) were given for 4 monthly cycles, followed by monthly D for 8 monthly cycles. SBRT to 2-5 lesions was administered during cycle 2. The safety of the TTC was the primary endpoint of the phase I and was evaluated through assessment of Grade 3-5 TTC-related adverse events (AE), based on CTCAE (v 4.03). The primary endpoint of the phase II portion was 6-month progression free survival (PFS), with a predetermined 6-month PFS (6moPFS) rate greater than 27% considered as a positive signal to conduct further research on this combination. Results: A total of 33 evaluable patients were recruited (study accrual was interrupted by the COVID pandemic). The table describes patients’ characteristics. Patients had received 1, 2 and 3 prior systemic therapy lines in 48%, 21% and 9% of the cases, including 6 (18%) patients who had received prior anti-PD-1/L1 or anti-CTLA-4 therapies. The median prescribed and maximum SBRT doses were 45 Gy (range: 18-50) and 52.3 Gy (range: 28.1-69) in 3-5 fractions, respectively Fourteen patients (42%) had Grade ≥ 3 AE attributable to D and T. Only 1 patient developed Grade ≥ 3 AE attributable to SBRT. This patient, who had mucosal radionecrosis after re-irradiation and refused surgical debridement and flap reconstruction, specifically developed 2 Grade 3, 1 Grade 4 and 1 Grade 5 AE. Our primary efficacy endpoint, 6moPFS, was 69.7% (95% CI: 55.6-87.3). Median PFS was 11.9 months (6.94-14.5) and median OS was 25.1 months (17.9-28.4). Rates of complete response, partial response, stable disease and progressive disease were 9%, 21%, 33% and 12%, respectively, with 8 (24%) patients with no evaluable non-SBRT treated lesion. Conclusions: The addition of SBRT to dual-checkpoint inhibition led to 1 (3%) additional patient developing severe AE. Best response rates were encouraging. Our primary efficacy outcome, 6mo PFS was attained and was higher than what was expected in this patient population. Clinical trial information: NCT03283605 . [Table: see text]
DNA methylation patterns between tissue and blood samples in ovarian cancer.
Authors: Hao Wen, Zheng Feng, Huijuan Ge, Yanan Wang, Jingshu Wang, Xiaoran Sun, Bo Yang, Chenlian Quan, Xiaoyan Zhou, Xiaohua Wu
Journal: Journal of Clinical Oncology (2023)

5558 Background: Altered DNA methylation pattern, with functional consequences in the activity of key carcinogenic pathways, has been shown to be involved in the carcinogenesis of ovarian cancer. Tumor DNA is released into the blood via apoptosis or necrosis. Therefore, cell-free DNA (cfDNA) methylation alteration can also be detected in blood, which has shown promising performance in ovarian cancer early detection and prognostication. However, the difference of DNA methylation patterns between the tissue and blood samples of ovarian cancer is still unclear. Methods: PERCEIVE-I study (NCT04903665) is a prospective study aimed at the early detection of gynecological malignancies. Blood and paired tissue samples from this study were collected at the Fudan University Shanghai Cancer Center. Blood samples from age-matched non-cancer controls were also collected. All the blood and paired tissue samples were sequenced by a target methylation panel covering ~490,000 CpG sites. Finally, The ovarian cancer methylation patterns were analyzed based on 11 paired cancer-adjacent tissue samples and 170 blood samples (cancer, n=48; non-cancer control, n=122). Results: In total, 7,225 differentially methylated blocks (DMBs) were identified by comparing cancer and adjacent tissues, with 5,093 hypomethylated and 2,132 hypermethylated. By contrast, there were 5,853 hypomethylated and 8,685 hypermethylated DMBs in cancer blood samples compared with non-cancer controls. Among the 7,225 DMBs in tissues, 3,962 (54.8%) blocks were also observed to be altered in blood samples, including 2,354 hypomethylated blocks and 1,114 hypermethylated blocks. GO analysis revealed that these hypomethylated blocks were mainly associated with functions such as regulation of synaptic membrane and DNA-binding transcription activator activity, while the hypermethylated blocks were mainly enriched in the pattern specification process, transcription factor complex, and the DNA-binding transcription activator activity. The alteration of the above 3,962 DMBs in tissue were highly correlated with the alteration in blood (correlation coefficient of 0.71, 0.50, 0.73 and 0.73 for stage I-IV, respectively). Furthermore, in patients carrying germline BRCA1/2 mutations (n=11), most of the above DMBs were not significantly different from those without germline BRCA1/2 mutations (n=37). Conclusions: In this study, we demonstrated that blood DNA methylation alteration was highly consistent with tissue DNA methylation alteration in ovarian cancer, indicating the sustained release of DNA methylation signals from the primary cancer sites. These results suggest that cfDNA methylation can be used as reliable biomarkers for the early detection of ovarian cancer. Clinical trial information: NCT04903665 .
A retrospective real-world study of nimotuzumab combined with chemotherapy for advanced pancreatic cancer.
Authors: Yinying Wu, Xuyuan Dong, EnXiao Li, Yangwei Fan, Danfeng Dong, Yu Shi, Meichen Wang, Nan Yang, Fengyun Ou, Jia Wang, Yuqian Yang
Journal: Journal of Clinical Oncology (2023)

e16271 Background: Existing treatment options including gemcitabine-based therapy and 5FU-based chemotherapy have limited prognostic impact in advanced pancreatic cancer (APC): the median overall survival (mOS) was 6-11 months for 1 st line therapy and 4-9 months for 2 nd line therapy. Nimotuzumab (nimo), anti-EGFR monoclonal antibody, had been shown to be more effective against APC in two previous studies, PCS07 (a phase II study in Germany) and NOTABLE study (a phase III study in China). Although the NOTABLE study obtained an encouraging result in China, it focused on a narrow population, KRAS wild-type patients. This study aimed to explore the efficacy and safety of nimo in the real-world population with APC. Methods: In this retrospective observational study, patients with APC were treated with nimo and followed up in a real-world clinical setting. Demographic and clinical data of these patients were collected from electronic medical records of First Affiliated Hospital of Xi’an Jiaotong University from April 2018 to June 2022. The primary efficacy endpoint was overall survival. Results: A total of 104 patients (median age was 60.5 years, range 34-84) treated with nimo and chemotherapy were analyzed. Among them, 11 (10.6%) were in stage II (AJCC 8 th edition), 23 (22.1%) were in stage III, and 70(67.3%) were in stage IV. The treatment regimen included gemcitabine plus nab-paclitaxel (AG, 80.77%), gemcitabine plus S-1 (GS, 10.58%) and others. The dosage of nimo was 200-400mg weekly, of which above 50% of patients received nimo 400 mg weekly. About 66 (63.5%) patients received nimo as 1 st line therapy and 38 (36.5%) patients as 2 nd line therapy. Up to July 5, 2022, the median follow-up time was 8.12 months and the mOS was not reached. The 1-year and 2-year OS rate were 80.2% and 74.4%, respectively. Further subgroup analysis showed that the mOS was also not reached in 1 st line treatment of nimo (median follow-up time 8.77 months) as well as the 2 nd line treatment of nimo (median follow-up time 7.62 months), showing a potential survival benefit. No grade 3 or above toxicities were observed. Conclusions: AG regimen was the most common therapy in clinical practice in China. The real world study displayed the addition of nimo would prolong the survival for APC, with a good safety profile.